Variant rs1805414 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001618.4(PARP1):c.852T>C(p.Ala284=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,612,866 control chromosomes in the GnomAD database, including 115,585 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14757 hom., cov: 33)

Exomes 𝑓: 0.36 ( 100828 hom. )

Consequence

PARP1
NM_001618.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.58

Variant links:

Genes affected

PARP1 (HGNC:270): (poly(ADP-ribose) polymerase 1) This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes. [provided by RefSeq, Jul 2008]

PARP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-2.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARP1	NM_001618.4 linkuse as main transcript	c.852T>C	p.Ala284=	synonymous_variant	7/23	ENST00000366794.10	NP_001609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARP1	ENST00000366794.10 linkuse as main transcript	c.852T>C	p.Ala284=	synonymous_variant	7/23	1	NM_001618.4	ENSP00000355759	P1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64471

AN:

151942

Hom.:

14726

Cov.:

show subpopulations

Gnomad AFR

AF:

0.542

Gnomad AMI

AF:

0.215

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.401

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.396

GnomAD3 exomes

AF:

0.426

AC:

107127

AN:

251338

Hom.:

25452

AF XY:

0.413

AC XY:

56066

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.553

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.813

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.408

Gnomad NFE exome

AF:

0.338

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.358

AC:

523678

AN:

1460806

Hom.:

100828

Cov.:

AF XY:

0.357

AC XY:

259707

AN XY:

726764

show subpopulations

Gnomad4 AFR exome

AF:

0.559

Gnomad4 AMR exome

AF:

0.538

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.793

Gnomad4 SAS exome

AF:

0.369

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.377

GnomAD4 genome

AF:

0.425

AC:

64564

AN:

152060

Hom.:

14757

Cov.:

AF XY:

0.429

AC XY:

31862

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.543

Gnomad4 AMR

AF:

0.458

Gnomad4 ASJ

AF:

0.328

Gnomad4 EAS

AF:

0.807

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.401

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.396

Alfa

AF:

0.361

Hom.:

6098

Bravo

AF:

0.439

Asia WGS

AF:

0.546

AC:

1900

AN:

3478

EpiCase

AF:

0.320

EpiControl

AF:

0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.037

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over